This study investigates the potential antituberculosis activity of genistein, a soy-derived isoflavone, through its interaction with Toll-like receptor 2 (TLR2) using in-silico methods. Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the deadliest infectious diseases globally, with rising cases of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB complicating treatment. TLR2 plays a critical role in the host immune response by recognizing Mtb cell wall components and activating signaling pathways that promote inflammation and bacterial clearance. Molecular docking studies demonstrated a strong binding affinity between genistein and TLR2, with a Vina score of -8.0 kcal/mol. Genistein interacted with key amino acid residues in the receptor's binding pocket, including ILE689, HIS697, TRP712, and ASP730. Further Absorption Distribution Metabolism Excretion (ADME) and toxicity predictions revealed that genistein undergoes extensive metabolism, generating 19 potential metabolites. Pharmacokinetic assays indicated that metabolites 7, 9, 15, 16, and 19 exhibited high Caco-2 cell line permeability, suggesting strong potential for oral bioavailability. However, metabolites 3, 5, 9, 13, 15, and 17 showed mutagenic potential in AMES tests, while metabolites 2, 5, 8, 10, 13, 15, and 17 displayed hepatotoxicity. Despite these risks, certain metabolites demonstrated favorable safety profiles, with LD50 values exceeding 2700 mg/kg. These findings suggest that genistein and its metabolites hold promise as complementary agents in TB treatment by modulating TLR2-mediated immune responses. However, further experimental validation and optimization are required to ensure efficacy and safety.